Trace metals such as zinc and manganese are known to be essential to the normal development of bones and teeth although their role in the biomineralization process has not been defined, On the other hand, non- essential metals like cadmium, can have severe deleterious effects on these tissues and have been linked to a number of osteopathic and dental disease states including osteomalacia, osteoporosis, and caries. The long-term objective of the proposed research is to gain a detailed understanding of metal metabolism in cells undergoing biological mineralization using growth plate chondrocytes as the primary model system. With better knowledge concerning the way in which trace metals are metabolized by mineralized tissues, a more direct assessment of their role in the development of these tissues can be made. Special attention will be focused on: 1) identification and characterization of metal binding proteins from growth plate chondrocytes, 2) uptake kinetics and intracellular partitioning of metal ions in chondrocyte cell cultures, and 3) the effect of essential and toxic metal ions on biochemical parameters critical to biomineralization. A range of metal ions of biological and toxicological importance including Zn, Mn, Al, Cd, and Pb will be used in these studies. Critical findings with the chondrocyte culture system will be tested in other mineralizing cell model systems such as ROS 17/2.8 cells and osteoblast-like MC3T3-E1 cells so that broader principles of metal metabolism and their roles in mineralized tissues can be identified. It is expected that these studies will lead directly to the development of better therapeutic measures for treatment of trace metal deficiencies and metal-induced disease states of calcified tissues.